Editing Chemotaxis (section)

== Bacterial chemotaxis—general characteristics ==<!-- This section is linked from [[Random walk]] -->
[[File:ChtxCCW CW (Fixed).png|right|350 px|<div style="text-align: center;border:none">Correlation of swimming behaviour and flagellar rotation</div>]]
Some [[bacteria]], such as ''[[Escherichia coli|E. coli]]'', have several [[flagellum|flagella]] per cell (4–10 typically). These can rotate in two ways:
# Counter-clockwise rotation aligns the flagella into a single rotating bundle, causing the bacterium to swim in a straight line; and
# Clockwise rotation breaks the flagella bundle apart such that each flagellum points in a different direction, causing the bacterium to tumble in place.<ref>{{cite journal | vauthors = Yuan J, Fahrner KA, Turner L, Berg HC | title = Asymmetry in the clockwise and counterclockwise rotation of the bacterial flagellar motor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 29 | pages = 12846–9 | date = July 2010 | pmid = 20615986 | pmc = 2919929 | doi = 10.1073/pnas.1007333107 | bibcode = 2010PNAS..10712846Y | doi-access = free }}</ref>
The directions of rotation are given for an observer outside the cell looking down the flagella toward the cell.<ref>{{Cite web|url=https://www.physik.uni-muenchen.de/lehre/vorlesungen/wise_16_17/Biophysics_of_Systems/013_BakterChemotaxis_DB_WS16.pdf |archive-url=https://web.archive.org/web/20170506024623/http://www.physik.uni-muenchen.de/lehre/vorlesungen/wise_16_17/Biophysics_of_Systems/013_BakterChemotaxis_DB_WS16.pdf |archive-date=2017-05-06 |url-status=live|title=Bacterial Chemotaxis}}</ref>

=== Behavior ===
The overall movement of a bacterium is the result of alternating tumble and swim phases, called [[run-and-tumble motion]].<ref>{{cite journal | vauthors = Berg HC, Brown DA | s2cid = 1909173 | title = Chemotaxis in Escherichia coli analysed by Three-dimensional Tracking | journal = Nature | volume = 239 | issue = 5374 | pages = 500–504 | date = October 1972 | doi = 10.1038/239500a0 | pmid = 4563019 | bibcode = 1972Natur.239..500B }}</ref> As a result, the trajectory of a bacterium swimming in a uniform environment will form a [[random walk]] with relatively straight swims interrupted by random tumbles that reorient the bacterium.<ref>{{cite journal | vauthors = Sourjik V, Wingreen NS | title = Responding to chemical gradients: bacterial chemotaxis | journal = Current Opinion in Cell Biology | volume = 24| issue = 2| pages = 262–268 | date = April 2012 | doi = 10.1016/j.ceb.2011.11.008 | pmid = 22169400 | pmc = 3320702 }}</ref> Bacteria such as ''[[Escherichia coli|E. coli]]'' are unable to choose the direction in which they swim, and are unable to swim in a straight line for more than a few seconds due to rotational [[diffusion]]; in other words, bacteria "forget" the direction in which they are going. By repeatedly evaluating their course, and adjusting if they are moving in the wrong direction, bacteria can direct their random walk motion toward favorable locations.<ref>{{cite book| vauthors = Berg HC |title=Random walks in biology|year=1993|pages=83–94|publisher=Princeton Univ. Press|location=Princeton, NJ|isbn=978-0-691-00064-0|edition=Expanded, rev.}}</ref>

In the presence of a chemical [[gradient]] bacteria will chemotax, or direct their overall motion based on the gradient. If the bacterium senses that it is moving in the correct direction (toward attractant/away from repellent), it will keep swimming in a straight line for a longer time before tumbling; however, if it is moving in the wrong direction, it will tumble sooner. Bacteria like ''[[Escherichia coli|E. coli]]'' use temporal sensing to decide whether their situation is improving or not, and in this way, find the location with the highest concentration of attractant, detecting even small differences in concentration.<ref>{{cite journal |vauthors= Sourjik V, Wingreen N|date=April 2012|title=Responding to Chemical Gradients: Bacterial Chemotaxis |journal= Current Opinion in Cell Biology|volume=24 |issue= 2|pages=262–8|doi=10.1016/j.ceb.2011.11.008|pmid= 22169400|pmc=3320702}}</ref>

This biased random walk is a result of simply choosing between two methods of random movement; namely tumbling and straight swimming.<ref>{{cite journal | vauthors = Macnab RM, Koshland DE | title = The gradient-sensing mechanism in bacterial chemotaxis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 69 | issue = 9 | pages = 2509–2512 | date = September 1972 | pmid = 4560688 | pmc = 426976 | doi = 10.1073/pnas.69.9.2509 | doi-access = free | bibcode = 1972PNAS...69.2509M }}</ref> The helical nature of the individual flagellar filament is critical for this movement to occur. The protein structure that makes up the flagellar filament, [[flagellin]], is conserved among all flagellated bacteria.<ref>{{cite journal | vauthors = Nedeljković M, Sastre DE, Sundberg EJ | title = Bacterial Flagellar Filament: A Supramolecular Multifunctional Nanostructure | journal = International Journal of Molecular Sciences | volume = 22 | issue = 14 | pages = 7521 | date = July 2021 | pmid = 34299141 | pmc = 8306008 | doi = 10.3390/ijms22147521 | doi-access = free }}</ref> Vertebrates seem to have taken advantage of this fact by possessing an immune receptor ([[Toll-like receptor|TLR5]]) designed to recognize this conserved protein.<ref>{{cite journal | vauthors = Zhong M, Yan H, Li Y | title = Flagellin: a unique microbe-associated molecular pattern and a multi-faceted immunomodulator | journal = Cellular & Molecular Immunology | volume = 14 | issue = 10 | pages = 862–864 | date = October 2017 | pmid = 28845044 | pmc = 5649114 | doi = 10.1038/cmi.2017.78 }}</ref>

As in many instances in biology, there are bacteria that do not follow this rule. Many bacteria, such as ''Vibrio'', are monoflagellated and have a single flagellum at one pole of the cell. Their method of chemotaxis is different. Others possess a single flagellum that is kept inside the cell wall. These bacteria move by spinning the whole cell, which is shaped like a corkscrew.<ref>{{cite book | vauthors = Berg HC | title=''E. coli'' in motion | year=2003 | isbn = 978-0-387-00888-2 |publisher=Springer | location=New York, NY }}{{page needed|date=March 2017}}</ref>{{page needed|date=March 2017}}

===Signal transduction===
[[Image:ChtxAspRec.png|right|350 px|<div style="text-align: center;border:none">Domain structure of chemotaxis receptor for Asp</div>]]
Chemical gradients are sensed through multiple [[transmembrane receptor]]s, called methyl-accepting chemotaxis proteins (MCPs), which vary in the molecules that they detect.<ref name=":1"/> Thousands of MCP receptors are known to be encoded across the bacterial kingdom.<ref>{{cite journal | vauthors = Galperin MY | title = A census of membrane-bound and intracellular signal transduction proteins in bacteria: bacterial IQ, extroverts and introverts | journal = BMC Microbiology | volume = 5 | pages = 35 | date = June 2005 | pmid = 15955239 | pmc = 1183210 | doi = 10.1186/1471-2180-5-35 | doi-access = free }}</ref> These receptors may bind attractants or repellents directly or indirectly through interaction with proteins of [[periplasmatic space]].<ref>{{Cite book| vauthors = Auletta G |title=Cognitive Biology: Dealing with Information from Bacteria to Minds|publisher=Oxford University Press|year=2011|isbn=978-0-19-960848-5|location=United States|pages=266}}</ref> The signals from these receptors are transmitted across the [[plasma membrane]] into the [[cytosol]], where ''[[Che proteins]]'' are activated.<ref name="ReferenceA">{{cite journal | vauthors = Falke JJ, Bass RB, Butler SL, Chervitz SA, Danielson MA | title = The two-component signaling pathway of bacterial chemotaxis: a molecular view of signal transduction by receptors, kinases, and adaptation enzymes | journal = Annual Review of Cell and Developmental Biology | volume = 13 | pages = 457–512 | date = 1997 | pmid = 9442881 | pmc = 2899694 | doi = 10.1146/annurev.cellbio.13.1.457 }}</ref> The Che proteins alter the tumbling frequency, and alter the receptors.<ref name="ReferenceA"/>

====Flagellum regulation====
The proteins CheW and CheA bind to the receptor. The absence of receptor activation results in [[phosphorylation|autophosphorylation]] in the [[histidine kinase]], CheA, at a single highly conserved histidine residue.<ref>{{cite web|url=https://www.youtube.com/watch?v=h4lv7cBYVug| archive-url=https://web.archive.org/web/20150711181802/https://www.youtube.com/watch?v=h4lv7cBYVug| archive-date=2015-07-11 | url-status=dead|title=Chemotaxis|last=ToxCafe|date=2 June 2011|access-date=March 23, 2017|via=YouTube}}</ref>{{better source needed|date=March 2017}} CheA, in turn, transfers phosphoryl groups to conserved aspartate residues in the response regulators CheB and CheY; CheA is a histidine kinase and it does not actively transfer the phosphoryl group, rather, the response regulator [[Protein-glutamate methylesterase|CheB]] takes the phosphoryl group from CheA.{{citation needed|date=March 2017}} This mechanism of signal transduction is called a [[two-component regulatory system|two-component system]], and it is a common form of signal transduction in bacteria.{{citation needed|date=March 2017}} CheY induces tumbling by interacting with the flagellar switch protein FliM, inducing a change from counter-clockwise to clockwise rotation of the flagellum. Change in the rotation state of a single flagellum can disrupt the entire flagella bundle and cause a tumble.{{citation needed|date=March 2017}}

====Receptor regulation====
[[Image:Chtxbactsign1.png|right|450 px|<div style="text-align: center;border:none">Signalling pathways of E.coli</div>]]
CheB, when activated by CheA, acts as a [[demethylase|methylesterase]], removing methyl groups from [[glutamate]] residues on the [[cytosol]]ic side of the receptor; it works antagonistically with CheR, a methyl[[transferase]], which adds methyl residues to the same glutamate residues.<ref name=":1" /> If the level of an attractant remains high, the level of phosphorylation of CheA (and, therefore, CheY and CheB) will remain low, the cell will swim smoothly, and the level of methylation of the MCPs will increase (because CheB-P is not present to demethylate).<ref name=":1">{{cite journal | vauthors = Wadhams GH, Armitage JP | title = Making sense of it all: bacterial chemotaxis | journal = Nature Reviews. Molecular Cell Biology | volume = 5 | issue = 12 | pages = 1024–1037 | date = December 2004 | pmid = 15573139 | doi = 10.1038/nrm1524 | s2cid = 205493118 }}</ref> The MCPs no longer respond to the attractant when they are fully methylated; therefore, even though the level of attractant might remain high, the level of CheA-P (and CheB-P) increases and the cell begins to tumble.<ref name=":1"/> The MCPs can be demethylated by CheB-P, and, when this happens, the receptors can once again respond to attractants.<ref name=":1" /> The situation is the opposite with regard to repellents: fully methylated MCPs respond best to repellents, while least-methylated MCPs respond worst to repellents.{{citation needed|date=March 2017}} This regulation allows the bacterium to 'remember' chemical concentrations from the recent past, a few seconds, and compare them to those it is currently experiencing, thus 'know' whether it is traveling up or down a gradient.
<ref>{{Cite book| vauthors = Shu C, Chen PC, Fung YC |title=An Introductory Text to Bioengineering (Advanced Series in Biomechanics - Vol. 4)|publisher=World Scientific Publishing Co. Pte. Ltd.|year=2008|isbn=9789812707932|location=Singapore|pages=418}}</ref> that bacteria have to chemical gradients, other mechanisms are involved in increasing the absolute value of the sensitivity on a given background. Well-established examples are the ultra-sensitive response of the motor to the CheY-P signal, and the clustering of chemoreceptors.<ref>{{cite journal | vauthors = Cluzel P, Surette M, Leibler S | s2cid = 5334523 | title = An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells | journal = Science | volume = 287 | issue = 5458 | pages = 1652–5 | date = March 2000 | pmid = 10698740 | doi = 10.1126/science.287.5458.1652 | bibcode = 2000Sci...287.1652C }}</ref><ref>{{cite journal | vauthors = Sourjik V | title = Receptor clustering and signal processing in E. coli chemotaxis | journal = Trends in Microbiology | volume = 12 | issue = 12 | pages = 569–76 | date = December 2004 | pmid = 15539117 | doi = 10.1016/j.tim.2004.10.003 | citeseerx = 10.1.1.318.4824 }}</ref>